Changes in Alternative Splicing as Pharmacodynamic Markers for Sudemycin D6

  • Biomark Insights. 2017 Sep 12:12:1177271917730557. doi: 10.1177/1177271917730557.
Morgan Thurman  1 ,  Jacob van Doorn  1 ,  Barbara Danzer  1 ,  Thomas R Webb  1 ,  Stefan Stamm  1
Affiliations
  • 1. University of Kentucky, Lexington, KY, USA.
PMID: 28932105 DOI: 10.1177/1177271917730557
Abstract

Objective: The aim of the study was to define pharmacodynamic markers for sudemycin D6, an experimental Cancer drug that changes alternative splicing in human blood.

Methods: Blood samples from 12 donors were incubated with sudemycin D6 for up to 24 hours, and at several time points total RNA from lymphocytes was prepared and the pre-messenger RNA (mRNA) splicing patterns were analyzed with reverse transcription-polymerase chain reaction.

Results: Similar to immortalized cells, blood lymphocytes change alternative splicing due to sudemycin D6 treatment. However, lymphocytes in blood respond slower than immortalized cultured cells.

Conclusions: Exon skipping in the DUSP11 and SRRM1 pre-mRNAs are pharmacodynamic markers for sudemycin D6 treatment and show effects beginning at 9 hours after treatment.

Keywords
Alternative splicing; lymphocytes RNA; splicing inhibition; sudemycin.
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